Alzheimer's DiseasePhase 2MAyflOwer RoADNCT01677754
A Study of RO4602522 in Participants With Moderate Severity Alzheimer Disease on Background Alzheimer Disease Therapy
A Phase 2 study testing RO4602522, Donepezil and Memantine in people with Alzheimer's Disease, run by Hoffmann-La Roche at 142 sites in 12 countries.
Trial summary
This Phase II, multicenter, randomized, double-blind, parallel-group, placebo-controlled study will evaluate the efficacy and safety of RO4602522 in participants with moderate severity Alzheimer's disease. Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- RO4602522, Donepezil and Memantine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 542 participants
- Where
- 142 sitesin 12 countries
- Study dates
- 24 Oct 2012to 12 Jun 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Probable Alzheimer disease, based on the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS)/Alzheimer's Disease and Related Disorders Association (ADRDA) and Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV-TR) criteria
- Mini-Mental State Exam (MMSE) score at screening between 13 and 20, inclusive
- Body mass index (BMI) between 18 and 36 kilograms per square meter (kg/m^2) (inclusive) at screening
- Modified Hachinski Ischemia Score of less than or equal to (</=) 4
- Participants with Cornell Scale for Depression in Dementia (CSDD) scores </= 13 at screening
- Receiving treatment with donepezil, rivastigmine, galantamine or any AChEIs in combination with memantine for at least 4 months before screening, with their dose and formulation stabilized at least 3 months before screening. All formulation and dosages are allowed except donezepil 23 mg (alone or in combination)
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- Females of childbearing potential must have a negative pregnancy test and must agree to use effective contraception
- Generally healthy and ambulatory or ambulatory-aided (i.e., walker or cane)
- Have a reliable caregiver or some other identified responsible person who has frequent contact with the participant
Who cannot join
- Any neurological or psychiatric condition that may occur currently or during the course of the study that can impair cognition or functioning that is not associated with Alzheimer's disease
- Background of mental retardation
- Uncontrolled behavioral symptoms incompatible with compliance or evaluability
- Alcohol and/or substance abuse or dependence (DSM-IV-TR) in the past 2 years, except nicotine use which is allowed. However, smokers treated with nicotine replacement therapy or bupropion are excluded
- Unstable or poorly controlled hypertension as assessed by the investigator regardless of whether or not the participant is taking antihypertensive medications
- Unstable or clinically significant cardiovascular disease that could be expected to progress, recur, or change during study period to such an extent that it could bias the assessment of the clinical or mental status of the participant
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- Inadequate hepatic, renal or thyroid function
- Positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
- Poorly controlled diabetes (glycosylated hemoglobin [HbA1c] greater than or equal to [>/=] 9 percent at screening)
- Requiring nursing home care. Participants living in assisted living facilities are allowed if a reliable caregiver is available (see inclusion criteria)
- Current treatment for Alzheimer's disease other than those listed in inclusion criteria
- Participation at any time in an active Alzheimer's disease vaccine study
- Participation in a passive Alzheimer's disease immunization study less than 1 year before screening except for a) participants where documented medical history indicate that they were randomized to the placebo group in these studies, b) participants treated with bapineuzumab where a 6-month exclusion period applies
- Recent (</= 12 weeks) or concomitant use of other Monoamine oxidase inhibitors (selective or not) including selegiline or rasagiline
- Antidepressant treatments are not allowed except for citalopram up to 20 mg daily, escitalopram up to 10 mg daily, paroxetine up to 30 mg daily, sertraline up to 100 mg daily and trazodone up to 100 mg daily. If treated with one of these antidepressants, the treatment should be present for at least 6 weeks at screening. All other antidepressants including other SSRIs, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), St. John's wort and bupropion are excluded
- Anti-psychotic use within 4 weeks before screening is not permitted except risperidone up to 1.5 mg/day, quetiapine up to 100 milligrams per day (mg/day), olanzapine up to 5 mg/day, and aripiprazole up to 10 mg daily
- Anxiolytics/ hypnotics use is not permitted except for benzodiazepines of short or intermediate half-life for anxiety/sleeping disorders. Zolpidem (up to 5 mg/day), zopiclone (up to 7.5 mg/day), eszopiclone (up to 2 mg/day), trazodone (up to 50 mg/day, at bedtime) or zaleplon (up to 5 mg/day) is permitted for insomnia
- Anti-Parkinson's agents within 2 weeks before screening are not permitted
- Recent (less than 4 weeks prior to screening) or concomitant use of anticonvulsants
- Anticholinergics/ antihistaminics within 2 weeks before screening are not permitted, except i) if used episodically more than 3 days before the screening cognitive measurement, ii) non-sedating antihistaminic medications (without anticholinergic effects such as cetirizine) or peripheral anticholinergics without central anticholinergic effects (such as, trospium for the treatment of hyperactive bladder), which are permitted
- Recent (less than 1 week prior to screening) or concomitant use of opioid drugs (tramadol, methadone, propoxyphene, or meperidine), cyclobenzaprine and dextromethorphan
- Concomitant use of sympathomimetic drugs, including sympathomimetics in local anesthetics and ephedra supplements
Trial locations and contacts
142 sites in 12 countries.
142 sites in 12 countries
United States42 sites
Albuquerque Neuroscience Inc.
Albuquerque, New Mexico, 87109
Advanced Research Center, Inc.;In-Patient Unit
Anaheim, California, 92801
Parkinson's Disease and Movement Disorders Center of Boca Raton
Boca Raton, Florida, 33486
Meridien Research
Brooksville, Florida, 34601
Alzheimer's Research & Clinical Programs
Charleston, South Carolina, 29425
Millennium Psychiatric Associates, LLC
Creve Coeur, Missouri, 63141
iResearch Atlanta
Decatur, Georgia, 30030
NeuroStudies.net, LLC
Decatur, Georgia, 30033
Brain Matters Research, Inc.
Delray Beach, Florida, 33445
Rhode Island Mood & Memory Research Institute
East Providence, Rhode Island, 02914
Memory Enhancement Center of America, Inc.
Eatontown, New Jersey, 07724
Alexian Brothers Neurosci Inst
Elk Grove Village, Illinois, 60007
Neurologic Consultants, P.A.
Fort Lauderdale, Florida, 33308
University of North Texas Health Science Center
Fort Worth, Texas, 76107
Neurology Center of North Orange County
Fullerton, California, 92835
Hattiesburg Clinic
Hattiesburg, Mississippi, 39401
Galiz Research, LLC
Hialeah, Florida, 33016
The Clinical Trial Center, LLC
Jenkintown, Pennsylvania, 19046
Torrance Clinical Research
Lomita, California, 90717
Miami Jewish Health Systems
Miami, Florida, 33137
Yale University School Of Medicine
New Haven, Connecticut, 06510
Louisiana Research Associates
New Orleans, Louisiana, 70114
New York University Medical Center;Child Study Center
New York, New York, 10016
Research Center for Clinical Studies, Inc.
Norwalk, Connecticut, 06851
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73112
Cutting Edge Research Group
Oklahoma City, Oklahoma, 73116
Medical Research Group of Central Florida
Orange City, Florida, 3273
Compass Research East, LLC
Orlando, Florida, 32806
Rhode Island Hospital
Providence, Rhode Island, 02903
Raleigh Neurology Associates
Raleigh, North Carolina, 27607-6520
Artemis Institute for Clinical Research, LLC
San Diego, California, 92103
Sharp Mesa Vista Hospital
San Diego, California, 92123
San Francisco Clinical Research Center
San Francisco, California, 94109
Neurological Research Inst
Santa Monica, California, 90025
Booker, J. Gary, MD, APMC
Shreveport, Louisiana, 71104-2136
Comprehensive Clinical Development, Inc.- St. Petersburg, FL
St. Petersburg, Florida, 33716
Richmond Behavioral Associates
Staten Island, New York, 10312
Axiom Clinical Research of Florida
Tampa, Florida, 33609
Northern Michigan Neurology
Traverse City, Michigan, 49684
Premiere Research Institute
West Palm Beach, Florida, 33407
PMG Research of Winston-Salem, LLC
Winston-Salem, North Carolina, 27103
Radiant Research, Inc.
Wyomissing, Pennsylvania, 19610
Canada16 sites
Jbn Medical Diagnostic Services Inc.
Burlington, Ontario, L7M 4Y1
Recherches Neuro-Hippocame
Gatineau, Quebec, J8T 8J1
Clinique Neuro Rive-Sud
Greenfield Park, Quebec, J4V 2J2
Capitol District Health Authority
Halilfax, Nova Scotia, B3H 2E1
True North Clinical Research Kentville
Kentville, Nova Scotia, B4N 4K9
Bruyere Continuing Care
Ottawa, Ontario, K1N 5C8
Ingram, Jennifer MD
Peterborough, Ontario, K9H 3S1
The Medical Arts Health Research Group
Powell River, British Columbia, V8A 3B6
CHU de Quebec - Hôpital de l' Enfant Jésus
Québec, G1J 1Z4
Institut Universitaire de gériatrie de Sherbrooke; Service de gériatrie/pavillon Argyll
Sherbrooke, Quebec, J1J 3H5
Toronto Memory Program (Neurology Research Inc.)
Toronto, Ontario, M3B 2S7
The Centre for Memory and Aging
Toronto, Ontario, M4G 3E8
Toronto Sunnybrook Hospital
Toronto, Ontario, M4N 3M5
Vancouver Hospital - UBC Hospital Site
Vancouver, British Columbia, V6T 2B5
McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric
Verdun, Quebec, H4H 1R3
Vancouver Island Health Authority
Victoria, British Columbia, V8R 1J8
France12 sites
Centre Hospitalier de la côte Basque
Bayonne, 64109
Hopital Neurologique Pierre Wertheimer
Bron, 69500
Hopital Nord Laënnec - CHU Nantes
Nantes, 44093
Hopital Cimiez; CMRR
Nice, 06003
Hôpital Lariboisière
Paris, 75475
Groupe Hospitalier Sud - Hôpital Xavier Arnozan
Pessac, 33604
Hôpital Maison Blanche
Reims, 51092
CHU Rennes - Hopital Hôtel Dieu
Rennes, 35064
CHU Toulouse - La Grave
Toulouse, 31059
CHU Tours - Hôpital Bretonneau
Tours, 37044
Hôpital de Brabois Adultes
Vandœuvre-lès-Nancy, 54511
Hopital des Charpennes
Villeurbanne, 69100
Spain12 sites
Hospital Perpetuo Socorro, Servicio de Geriatria
Albacete, 2006
CAE Oroitu
Barakaldo, Vizcaya, 48903
Fundació ACE
BArcelon, Barcelona, 08034
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Hospital General Universitario de Elche; Servicio de Farmacia
Elche, Alicante, 03203
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario Clínico San Carlos
Madrid, 28040
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222
Hospital Virgen del Puerto
Plasencia, Palencia, 10600
Hospital General De Catalunya; Servicio de Neurologia
Sant Cugat del Vallès, Barcelona, 8195
Hospital Universitario Virgen Macarena
Seville, Sevilla, 41071
Hospital Universitari i Politecnic La Fe
Valencia, 46026
Czechia10 sites
NEUROHK s.r.o.
Choceň, 565 01
P-P Klinika
Kladno, 272 80
Supervize s.r.o.
Kutna Hora - Vnitrni Mesto, 284 01
Clintrial,s.r.o.
Prague, 100 00
AD71 s.r.o.
Prague, 102 00
Psychiatry Trial s.r.o.
Prague, 158 00
Neurologicka ambulance
Prague, 16000
FORBELI s.r.o.
Prague, 165 00
Nemocnice Na Bulovce
Prague, 180 01
Thomayerova nemocnice
Praha 4 - Krc, 140 59
Australia9 sites
Box Hill Hospital; Eastern Clinical Research Unit
Box Hill, Victoria, 3128
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010
Central Coast Neurosciences Research
Erina, New South Wales, 2250
A.G.Mander Pty Ltd
Geelong, Victoria, 3220
Heidelberg Repatriation Hospital
Heidelberg, Victoria, 3084
Southern Neurology
Kogarah, New South Wales, 2217
Hollywood Specialist Centre
Nedlands, Western Australia, 6009
Neurodegenerative Disorders Research
Subiaco, Western Australia, 6008
Queen Elizabeth Hospital
Woodville, South Australia, 5011
Poland9 sites
Podlaskie Centrum Psychogeriatrii
Bialystok, 15-732
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-214
Specjal. Praktyka Lekarska; Prof. Grzegorz Opala
Katowice, 40-588
Centrum Medyczne Dendryt
Katowice, 40-684
NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek
Poznan, 61-289
NZOZ Syntonia
Pruszcz Gdański, 83-000
NZOZ Pro-Cordis Sopockie Centrum Bad. Kardiolog
Sopot, 81-717
mMED Maciej Czarnecki
Warsaw, 01-697
Instytut Psychiatrii i Neurologii
Warsaw, 02-957
South Korea9 sites
Dong-A University Hospital
Busan, 49201
Seoul National University Bundang Hospital
Gyeonggi-do, 13620
Ajou University Hospital
Gyeonggi-do, 443-380
Inha University Hospital; Pulmonary Medicine
Incheon, 400-711
Kyung Hee University Hospital
Seoul, 02447
Korea University Anam Hospital
Seoul, 02841
Severance Hospital, Yonsei University Health System
Seoul, 03722
Konkuk University Medical Center
Seoul, 05030
Samsung Medical Center
Seoul, 06351
Italy8 sites
Ente Ospedaliero Ospedali Galliera
Genoa, Liguria, 16128
Università degli Studi di Genova
Genoa, Liguria, 16132
Nuovo Ospedale Civile S.Agostino - Estense
Modena, Emilia-Romagna, 41126
Università degli studi di Perugia
Perugia, Umbria, 06126
Azienda Ospedaliero Universitaria Pisana; Uff. Sperim. Clin. U.O. Farmaceutica
Pisa, Tuscany, 56126
Policlinico Universitario Agostino Gemelli; Farmacia
Rome, Lazio, 00168
Fondazione Santa Lucia IRCCS
Rome, Lazio, 00179
Umberto I Policlinico di Roma-Università di Roma La Sapienza
Rome, Lazio, 00185
United Kingdom8 sites
Cognitive Treatment & Research Unit
Crowborough, TN6 1HB
Ninewells Hospital
Dundee, DD12 9SY
Glasgow Memory Clinic
Glasgow, G20 0XA
West London Cognitive Disorders Treatment and Research Unit; Lakeside Metal Health Unit
Isleworth, TW7 6FY
Institute of Psychiatry
London, SE5 8AF
Norwich Medical School
Norwich, NR4 7UY
Derriford Hospital
Plymouth, PL6 8DH
Memory Service North
Sheffield, S35 8QS
Germany5 sites
Gemeinschaftspraxis
Ellwangen, 73479
Henriettenstiftung Hannover
Hanover, 30559
ISPG - Institut fuer Studien zur Psychischen Gesundheit
Mannheim, 68165
Klinikum rechts der Isar der Technischen Universität München
München, 81675
Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung
Siegen, 57072
Sweden2 sites
Skanes Universitetssjukhus, Malmo Skanes Universitetssjukhus, Malmo
Malmö, 205 02
Karolinska Universitetssjukhuset Huddinge
Stockholm, 171 64
About this study
Official title: A Phase II, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Investigate the Efficacy and Safety of RO4602522 Added to Background Alzheimer's Disease Therapy in Patients With Moderate Severity Alzheimer's Disease
This Phase II, multicenter, randomized, double-blind, parallel-group, placebo-controlled study will evaluate the efficacy and safety of RO4602522 in participants with moderate severity Alzheimer's disease. Participants who are taking background therapy of acetylcholinesterase inhibitors (AChEI) alone or in combination with memantine for at least 4 months before screening will be randomized to receive either one of two doses of RO4602522 or placebo for 12 months.
- Conditions
- Alzheimer's Disease
- Being tested
- RO4602522, Placebo, Donepezil, Memantine, Rivastigmine
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO4602522Drug
Participants will receive RO4602522 orally once daily for 12 months.
PlaceboDrug
Participants will receive placebo for RO4602522 orally once daily for 12 months.
DonepezilDrug
Stable dose as background medication
MemantineDrug
Stable dose as background medication in combination with AChEIs
RivastigmineDrug
Stable dose as background medication
GalantamineDrug
Stable dose as background medication
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will receive placebo as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine. Receives: Drug: Placebo; Drug: Donepezil; Drug: Memantine; Drug: Rivastigmine; Drug: Galantamine |
| RO4602522 1 milligram (mg) | Experimental | Participants will receive RO4602522 1 mg as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine. Receives: Drug: RO4602522; Drug: Donepezil; Drug: Memantine; Drug: Rivastigmine; Drug: Galantamine |
| RO4602522 5 mg | Experimental | Participants will receive RO4602522 5 mg as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine. Receives: Drug: RO4602522; Drug: Donepezil; Drug: Memantine; Drug: Rivastigmine; Drug: Galantamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Behavior Subscale (ADAS-Cog-11) Score at Month 12
Measured: Baseline, Month 12
Secondary outcomes (18)
Percentage of Participants Achieving Response, Defined as an Increase From Baseline of Less Than or Equal to (<=) 4 Points in ADAS-Cog-11
Measured: Baseline, Month 12
Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Scale Score at Month 12
Measured: Baseline, Month 12
Change From Baseline in Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW) Score at Month 12
Measured: Baseline, Month 12
Percentage of Participants With Worsening in BEHAVE-AD-FW Score
Measured: Baseline to Month 12
Change From Baseline in Apathy Evaluation Scale (AES) Score at 12 months
Measured: Baseline, Month 12
Change From Baseline in Alzheimer's Disease Cooperative Study Clinician Global Impression of Change (ADCS-CGIC) Scale Score at 12 months
Measured: Baseline, Month 12
Percentage of Participants With Worsening in ADCS-CGIC Score
Measured: Baseline to Month 12
Change From Baseline in Global Deterioration Scale (GDS) Score at 12 months
Measured: Baseline, Month 12
Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score at 12 months
Measured: Baseline, Month 12
Percentage of Participants with Adverse Events
Measured: Baseline up to 13 months
Percentage of Participants with Change in Lens Opacity Grading
Measured: Baseline; Months 6, and 12
Percentage of Participants with Abnormal Visual Acuity Test Results
Measured: Baseline, Months 6, and 12
Change From Baseline in Michigan Neuropathy Screening Instrument Score
Measured: Baseline, Weeks 8, 18, 30, 44, 52, and at the last follow-up visit (12 weeks after last dose, up to 64 weeks)
Percentage of Participants Receiving Concomitant Medications
Measured: Baseline to 13 Months
Apparent Total Clearance of the Drug From Plasma After Administration of RO4602522
Measured: Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
Apparent Volume of Distribution at Steady State after Administration of RO4602522
Measured: Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
Area Under the Plasma Concentration-Time Curve of RO4602522
Measured: Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
Maximum Plasma Concentration of RO4602522
Measured: Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2012 (estimated)
- Study start24 Oct 2012
- Primary completion12 Jun 2015
- Study completion12 Jun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 542 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01677754
- Sponsor's protocol ID
- BP28248
- Other IDs
- 2012-000943-29
- Acronym
- MAyflOwer RoAD
- Status last verified
- May 2017
- First submitted
- 30 Aug 2012
- Last updated
- 30 May 2017
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Nave S, Doody RS, Boada M, Grimmer T, Savola JM, Delmar P, Pauly-Evers M, Nikolcheva T, Czech C, Borroni E, Ricci B, Dukart J, Mannino M, Carey T, Moran E, Gilaberte I, Muelhardt NM, Gerlach I, Santarelli L, Ostrowitzki S, Fontoura P. Sembragiline in Moderate Alzheimer's Disease: Results of a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (MAyflOwer RoAD). J Alzheimers Dis. 2017;58(4):1217-1228. doi: 10.3233/JAD-161309.
PubMed 28550255
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Investigate the Efficacy and Safety of RO4602522 Added to Background Alzheimer's Disease Therapy in Patients With Moderate Severity Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT01677754
- Acronym / sponsor ID
- MAyflOwer RoAD / BP28248
- Conditions
- Alzheimer's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 542 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 24 Oct 2012 (actual)
- Primary completion
- 12 Jun 2015 (actual)
- Study completion
- 12 Jun 2015 (actual)
- First posted
- 3 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase II, multicenter, randomized, double-blind, parallel-group, placebo-controlled study will evaluate the efficacy and safety of RO4602522 in participants with moderate severity Alzheimer's disease. Participants who are taking background therapy of acetylcholinesterase inhibitors (AChEI) alone or in combination with memantine for at least 4 months before screening will be randomized to receive either one of two doses of RO4602522 or placebo for 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo, Drug: Donepezil, Drug: Memantine, Drug: Rivastigmine, Drug: GalantamineParticipants will receive placebo as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine. |
| RO4602522 1 milligram (mg) | Experimental | Drug: RO4602522, Drug: Donepezil, Drug: Memantine, Drug: Rivastigmine, Drug: GalantamineParticipants will receive RO4602522 1 mg as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine. |
| RO4602522 5 mg | Experimental | Drug: RO4602522, Drug: Donepezil, Drug: Memantine, Drug: Rivastigmine, Drug: GalantamineParticipants will receive RO4602522 5 mg as add-on to a background therapy of AChEI (donepezil, rivastigmine, or galantamine) alone or in combination with memantine. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Probable Alzheimer disease, based on the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS)/Alzheimer's Disease and Related Disorders Association (ADRDA) and Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV-TR) criteria
- Mini-Mental State Exam (MMSE) score at screening between 13 and 20, inclusive
- Body mass index (BMI) between 18 and 36 kilograms per square meter (kg/m^2) (inclusive) at screening
- Modified Hachinski Ischemia Score of less than or equal to (</=) 4
- Participants with Cornell Scale for Depression in Dementia (CSDD) scores </= 13 at screening
Key exclusion criteria (22 listed)
- Any neurological or psychiatric condition that may occur currently or during the course of the study that can impair cognition or functioning that is not associated with Alzheimer's disease
- Background of mental retardation
- Uncontrolled behavioral symptoms incompatible with compliance or evaluability
- Alcohol and/or substance abuse or dependence (DSM-IV-TR) in the past 2 years, except nicotine use which is allowed. However, smokers treated with nicotine replacement therapy or bupropion are excluded
- Unstable or poorly controlled hypertension as assessed by the investigator regardless of whether or not the participant is taking antihypertensive medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RO4602522Participants will receive RO4602522 orally once daily for 12 months. | Drug | RO4602522 1 milligram (mg), RO4602522 5 mg |
| PlaceboParticipants will receive placebo for RO4602522 orally once daily for 12 months. | Drug | Placebo |
| DonepezilStable dose as background medication | Drug | Placebo, RO4602522 1 milligram (mg), RO4602522 5 mg |
| MemantineStable dose as background medication in combination with AChEIs | Drug | Placebo, RO4602522 1 milligram (mg), RO4602522 5 mg |
| RivastigmineStable dose as background medication | Drug | Placebo, RO4602522 1 milligram (mg), RO4602522 5 mg |
| GalantamineStable dose as background medication | Drug | Placebo, RO4602522 1 milligram (mg), RO4602522 5 mg |
Primary outcome
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Behavior Subscale (ADAS-Cog-11) Score at Month 12
Time frame: Baseline, Month 12
18 secondary outcomes
Percentage of Participants Achieving Response, Defined as an Increase From Baseline of Less Than or Equal to (<=) 4 Points in ADAS-Cog-11
Time frame: Baseline, Month 12
Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Scale Score at Month 12
Time frame: Baseline, Month 12
Change From Baseline in Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW) Score at Month 12
Time frame: Baseline, Month 12
Percentage of Participants With Worsening in BEHAVE-AD-FW Score
Time frame: Baseline to Month 12
Change From Baseline in Apathy Evaluation Scale (AES) Score at 12 months
Time frame: Baseline, Month 12
Change From Baseline in Alzheimer's Disease Cooperative Study Clinician Global Impression of Change (ADCS-CGIC) Scale Score at 12 months
Time frame: Baseline, Month 12
Percentage of Participants With Worsening in ADCS-CGIC Score
Time frame: Baseline to Month 12
Change From Baseline in Global Deterioration Scale (GDS) Score at 12 months
Time frame: Baseline, Month 12
Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score at 12 months
Time frame: Baseline, Month 12
Percentage of Participants with Adverse Events
Time frame: Baseline up to 13 months
Percentage of Participants with Change in Lens Opacity Grading
Time frame: Baseline; Months 6, and 12
Percentage of Participants with Abnormal Visual Acuity Test Results
Time frame: Baseline, Months 6, and 12
Change From Baseline in Michigan Neuropathy Screening Instrument Score
Time frame: Baseline, Weeks 8, 18, 30, 44, 52, and at the last follow-up visit (12 weeks after last dose, up to 64 weeks)
Percentage of Participants Receiving Concomitant Medications
Time frame: Baseline to 13 Months
Apparent Total Clearance of the Drug From Plasma After Administration of RO4602522
Time frame: Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
Apparent Volume of Distribution at Steady State after Administration of RO4602522
Time frame: Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
Area Under the Plasma Concentration-Time Curve of RO4602522
Time frame: Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
Maximum Plasma Concentration of RO4602522
Time frame: Day -1, pre-dose (0 hour) on Days 14, 28, 84, 168, 252, and 364; 1 to 2 hour post dose on Days 14, 84, 252; 2-4 and 5-6 hours post dose on Days 28, 168, and 364
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
- Derived from this study: PubMed 28550255Nave S, Doody RS, Boada M, Grimmer T, Savola JM, Delmar P, Pauly-Evers M, Nikolcheva T, Czech C, Borroni E, Ricci B, Dukart J, Mannino M, Carey T, Moran E, Gilaberte I, Muelhardt NM, Gerlach I, Santarelli L, Ostrowitzki S, Fontoura P. Sembragiline in Moderate Alzheimer's Disease: Results of a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (MAyflOwer RoAD). J Alzheimers Dis. 2017;58(4):1217-1228. doi: 10.3233/JAD-161309.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
142 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RO4602522, Donepezil and Memantine in people with Alzheimer's Disease, run by Hoffmann-La Roche at 142 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 142 sites in United States, Canada, France, Spain, Czechia and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Behavior Subscale (ADAS-Cog-11) Score at Month 12 (time frame: Baseline, Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01677754, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2017.